Cancer-associated fibroblasts (CAFs) play a critical linchpin behind the colorectal cancer liver metastasis (CRLM) and immunological escape by the aberrant deposition of extracellular matrix (ECM). Herein, we crafted an intricately designed biomimetic nanoparticle architecture (denoted as UDCA-Cu@DMSN-M) that leveraged dendritic mesoporous silica nanoparticle (DMSN) as a versatile scaffold to enable the encapsulation of copper ions (Cu 2+ ) and ursodeoxycholic acid (UDCA) in their intricate cavities, and camouflaged with CAF membrane (CAFM) to augment CAF-site targeting. To encapsulate, the judicious integration of a myriad of interdependent attributes into a single material has the potential to trigger a cascading “domino effect” that encompasses CAFs reprogramming, ECM process reversal, epithelial-mesenchymal transition (EMT) inhibition, and antitumor immunity reinvigorating, thereby paving the way for innovative and comprehensive cancer treatment paradigms. A biomimetic CAF membrane-camouflaged nanomedicine has been developed for colorectal cancer liver metastasis. This platform co-delivers copper ions and ursodeoxycholic acid to reprogram cancer-associated fibroblasts and boost antitumor immunity, achieving synergistic treatment cascade. • Construct CAF membrane-camouflaged UDCA-Cu@DMSN-M for precise CAF targeting. • Synergize cuproptosis and TGF-β degradation to reprogram CAFs & reverse ECM deposition. • Activate antitumor immunity, potently inhibit CRLM with good biocompatibility.
Wu et al. (Wed,) studied this question.
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